Lamin A/C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement

Background-Dilated cardiomyopathy is a form of heart muscle disease charact erized by impaired systolic function and ventricular dilation. Familial tra nsmission of the disease is frequently observed, and genetic heterogeneity is indicated by clinical and morphological variability in the disease pheno type. In the family MDDC1 reported here, the disease phenotype is severe an d characterized by an autosomal dominant pattern of transmission. In additi on, the majority of affected family members show signs of mild skeletal mus cle involvement. Methods and Results-On the basis of the clinical observation of both cardia c and skeletal muscle abnormalities in the MDDC1 family, the lamin A/C gene was examined in this kindred. Coding regions were polymerase chain reactio n-amplified from genomic DNA and sequenced. A single nucleotide deletion wa s identified within exon 6, and all affected individuals were found to be h eterozygous for this deletion. Conclusions-Heterozygosity for a single nucleotide deletion in exon 6 of la min A/C segregates with both the cardiac and skeletal abnormalities observe d in the MDDC1 family. (Circulation. 2000;101:473-476.).